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dc.contributor.supervisor Klonisch,Thomas (Human Anatomy & Cell Science) en
dc.contributor.author Glogowska, Aleksandra Maria
dc.date.accessioned 2010-09-14T14:35:10Z
dc.date.available 2010-09-14T14:35:10Z
dc.date.issued 2010-09-14T14:35:10Z
dc.identifier.citation Pyka J, Glogowska A., Dralle H., Hoang-Vu C., Klonisch T(2005).Cancer Res. Feb 15;65(4):1343-51. en
dc.identifier.citation Glogowska A, Klonisch T. EGF like - ligand in cancer (2007). Cancer encyclopedia. en
dc.identifier.citation Glogowska A, Pyka J , Kehlen A, Los M, Perumal P, Weber E, Dralle H, Hoang-Vu, Sheue –yann Cheng C, Klonisch T (2009) Neoplasia Oct;10(10):1120-30 en
dc.identifier.citation Klonisch T, Glogowska A, Gratao AA, Grzech M, Nistor A, Torchia M, Weber E, de Angelis MH, Rathkolb B, Cuong HV, Wolf E, Schneider MR (2009).FEBS Lett. Apr 17;583(8):1349-57 en
dc.identifier.uri http://hdl.handle.net/1993/4199
dc.description.abstract Epidermal Growth Factor (EGF) is a member of the EGF-like family. EGF binding to the Epidermal Growth Factor Receptor (EGFR) affects cell survival as well as proliferation, migration, and tissue differentiation. Over-expression along with ligand-induced activation of EGFR has been correlated with increased in vivo invasiveness of tumor cells and enhanced in vitro migration of cell lines. This in turn makes EGFR a very important target for cancer therapy. In our investigation we have discovered that the cytoplasmic domain of proEGF (proEGFcyt) has the ability to decrease proliferation and migration in thyroid carcinoma cell lines. We illustrated that proEGFcyt causes specific alterations in the microtubular (MT) phenotype and the composition of MT-associated proteins (MAP) in FTC-133 overexpressing proEGFcyt, a finding not observed in FTC-133 over-expressing a novel splice form of proEGFcyt with a deletion of the complete exon 23 (proEGFdel23) (Pyka et al., 2004). Here, we demonstrate that proEGFcyt suppresses motility and elastinolytic activity in human thyroid Ca cells as a result from reduced secretion of cath-L. This impaired the ability of thyroid Ca cells to penetrate elastin matrices. The reduction in cath-L secretion was as a result of an up-regulation of SNAP25, a member of the t-SNARE plasma membrane complex, which is involved in Ca2+-dependent exocytosis. Furthermore, we demonstrated that proEGFcyt-mediated silencing of UCH-L1 causes the decrease in EGFR due to enhanced EGFR ubiquitination. This correlated with altered proteasomal degradation and provides a unique new mechanism on how proEGFcyt can affect cell proliferation in human thyroid cancer cells. These studies identified novel functions of human proEGF as a bidirectional signaling molecule consisting of the known extracellular EGF domain which functions as the classical ligand and activator of EGFR-mediated cell growth and the proEGF cytoplasmic domain which has the ability to suppress migration and growth of human thyroid carcinoma cells. en
dc.format.extent 29038285 bytes
dc.format.mimetype application/pdf
dc.language.iso en_US
dc.rights info:eu-repo/semantics/openAccess
dc.subject Thyroid cancer en
dc.subject EGF en
dc.title Function of proEGF cytoplasmic domain in thyroid cancer en
dc.type info:eu-repo/semantics/doctoralThesis
dc.degree.discipline Human Anatomy and Cell Science en
dc.contributor.examiningcommittee Bergen, Hugo (Human Anatomy & Cell Science) Wilkins,John (Internal Medicine) Parkinson,Fiona(Pharmacology) Di Cristofano,Antonio (Albert Einstein College of Medicine) en
dc.degree.level Doctor of Philosophy (Ph.D.) en
dc.description.note October 2010 en


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